What is Isoniazid used for?

Isoniazid: An Introduction

Isoniazid, often known by its trade names such as Laniazid, Nydrazid, and Rimifon, is a cornerstone drug in the treatment of tuberculosis (TB). Tuberculosis is a bacterial infection caused by Mycobacterium tuberculosis, which primarily affects the lungs but can also impact other organ systems. First discovered in the 1950s, isoniazid has been a crucial part of the anti-tubercular regimen for over six decades. It targets the bacterial cell wall, rendering the bacteria unable to maintain its structure and leading to its eventual death.

Various research institutions, including the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), have conducted extensive studies on isoniazid. These studies have established its efficacy and safety profile. Isoniazid is classified as a bactericidal antibiotic and is indicated for both the treatment and prevention of TB. It is particularly effective in the initial phase of TB treatment, often used in combination with other drugs to prevent the emergence of drug-resistant strains.

Isoniazid Mechanism of Action

The primary mechanism of action of isoniazid involves the inhibition of mycolic acid synthesis. Mycolic acids are essential components of the mycobacterial cell wall, contributing to its durability and impermeability. Isoniazid acts as a prodrug, meaning it must be activated within the bacterial cell to exert its effect. The activation is carried out by the bacterial enzyme catalase-peroxidase, encoded by the katG gene.

Once activated, isoniazid forms a complex with NADH (nicotinamide adenine dinucleotide), which subsequently inhibits the enzyme InhA (enoyl-ACP reductase). This enzyme is crucial for the synthesis of mycolic acids. By blocking InhA, isoniazid disrupts the construction of the bacterial cell wall, leading to cell lysis and death. This bactericidal action is especially potent against actively dividing mycobacteria, making isoniazid an essential drug in the initial phase of TB treatment.

How to Use Isoniazid

Isoniazid is typically administered orally, although it can also be given via intramuscular injection in cases where oral administration is not feasible. The standard oral dose for adults is 300 mg daily, while pediatric doses are calculated based on body weight, generally around 10-15 mg/kg. For preventive (prophylactic) therapy, the drug is often prescribed for a period of six to nine months, while the treatment of active TB usually involves a combination regimen lasting six months or longer.

The onset of action for isoniazid is relatively swift, with peak plasma concentrations occurring within 1-2 hours after oral administration. However, its therapeutic effects in TB treatment are usually observed over a more extended period, necessitating prolonged use to ensure the complete eradication of the bacteria. Adherence to the prescribed regimen is crucial for the effectiveness of the treatment and to prevent the development of drug-resistant TB strains.

What is Isoniazid Side Effects

While isoniazid is generally well-tolerated, it can cause a range of side effects, some of which may be severe. The most common side effects include gastrointestinal disturbances such as nausea, vomiting, and loss of appetite. Additionally, patients may experience peripheral neuropathy, characterized by tingling or numbness in the extremities. This is due to the depletion of pyridoxine (vitamin B6), and it can be mitigated by concurrent administration of pyridoxine supplements.

More serious side effects include hepatotoxicity, which can range from mild elevations in liver enzymes to severe hepatitis and liver failure. Therefore, regular monitoring of liver function tests is recommended during isoniazid therapy. Allergic reactions, although rare, can also occur, manifesting as rash, fever, and in severe cases, anaphylaxis.

There are several contraindications for the use of isoniazid. It should be used with caution in patients with pre-existing liver disease, chronic alcohol use, or a history of previous adverse reactions to the drug. Additionally, it is contraindicated in patients with known hypersensitivity to isoniazid or any of its components.

What Other Drugs Will Affect Isoniazid

The pharmacokinetics and pharmacodynamics of isoniazid can be influenced by various other medications. For instance, concurrent use of rifampin, another antitubercular drug, can enhance the hepatotoxic potential of isoniazid. Therefore, liver function should be closely monitored when these drugs are used together.

Drugs that induce the cytochrome P450 system, such as phenytoin and carbamazepine, can decrease the plasma concentration of isoniazid, potentially reducing its effectiveness. Conversely, isoniazid can increase the plasma levels of these drugs, heightening the risk of toxicity. Patients on such medications may require dose adjustments and closer monitoring.

Alcohol consumption should be avoided during isoniazid therapy, as it can exacerbate liver damage. Additionally, antacids containing aluminum salts can impair the absorption of isoniazid if taken concurrently. It is advisable to administer isoniazid at least one hour before or two hours after taking antacids.

In summation, while isoniazid remains a vital drug in the fight against tuberculosis, its use requires careful consideration of potential side effects, drug interactions, and patient-specific factors. Ongoing research and vigilance in monitoring can help optimize its efficacy and safety, ensuring that it continues to save lives in the battle against TB.